RESUMEN
INTRODUCTION: Adequate suppression of physiologic myocardial glucose uptake is important to ensure the interpretability and diagnostic reliability of [18F]fluorodeoxyglucose (FDG) PET/CT studies performed in the context of cardiac inflammation and infection. This study describes our experience with 4 preparatory protocols used in our institution. METHODS: FDG PET/CT scans were performed according to 4 preparatory protocols (716 scans total), i.e. 6-h fast (group 1), low-carbohydrate diet plus 12-h fast (group 2), low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (15 IU/kg) (group 3), and low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (50 IU/kg) (group 4). Consecutive scans were retrospectively included from time frames during which the particular protocol was used. FDG uptake in normal myocardium was scored on a scale ranging from 0 (uptake less than that in the left ventricular blood pool) to 4 (diffuse uptake greater than that in the liver). Complete suppression was defined as uptake less than or equal to the blood pool (scores 0-1). RESULTS: Complete suppression was accomplished in 27% in group 1, 68% in group 2, 69% in group 3 and 81% in group 4. Complete suppression was significantly lower in group 1 compared with all other groups (P < 0.0001 for all comparisons) and significantly higher in group 4 compared with group 2 (P = 0.005) and group 3 (P = 0.007). Groups 2 and 3 did not differ significantly (P = 0.92). CONCLUSION: A total of 50 IU/kg single-dose heparin administration before FDG PET/CT in addition to a low-carbohydrate diet and prolonged fast significantly outperformed protocols with no or lower dose (15 IU/kg) heparin in completely suppressing myocardial glucose metabolism.
Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Glucosa , Heparina , Humanos , Miocardio , Radiofármacos , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
PURPOSE: FDG PET/CT has been of increasing interest in the diagnostic workup of prosthetic heart valve endocarditis (PVE). Some reports advocate later imaging time points to improve the diagnostic accuracy for PVE. In this study, we compared standard and late FDG PET/CT images in patients with a clinical suspicion of PVE. MATERIALS AND METHODS: Fourteen scans in 13 patients referred for FDG PET/CT for suspicion of PVE performed at standard (60 min post injection) and late (150 min post injection) time points were scored based on visual interpretation and semi-quantitatively with SUVmax and target-to-background ratio (TBR, defined as [SUVmax valve/SUVmean blood pool]). Final diagnosis was based on surgical findings in all cases of infection (n = 6) and unremarkable follow-up in all others (n = 8). RESULTS: Late images were more prone to false positive interpretation for both visual and semi-quantitative analyses. Visual analysis of the standard images yielded 1 false negative and 1 false positive result. On the late images, no scans were false negative but 5 scans were false positive. CONCLUSION: Late FDG PET/CT imaging for PVE seems prone to false positive results. Therefore, late imaging should be interpreted with caution.
Asunto(s)
Endocarditis Bacteriana/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana EdadAsunto(s)
Dispositivos de Terapia de Resincronización Cardíaca , Tomografía Computarizada por Emisión de Fotón Único Sincronizada Cardíaca , Insuficiencia Cardíaca/diagnóstico por imagen , Imagen de Perfusión Miocárdica , Flebografía , Tomografía Computarizada por Rayos X , Insuficiencia Cardíaca/terapia , HumanosRESUMEN
Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with 123I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.
RESUMEN
PURPOSE: Patients with increased inflammatory parameters, nonspecific signs and symptoms without fever and without a diagnosis after a variety of diagnostic procedures are a diagnostic dilemma and are referred to as having inflammation of unknown origin (IUO). The objective of this pilot study was to compare the cost-effectiveness of a diagnostic work-up/strategy with and without (18)F-FDG PET/CT in patients with IUO using a published dataset as a reference. METHODS: IUO patients without (18)F-FDG PET/CT (group A, 46 patients) and IUO patients referred for (18)F-FDG PET/CT (group B, 46 patients) were selected. IUO was defined as the combination of nonspecific signs and symptoms and a prolonged erythrocyte sedimentation rate (ESR), defined as ≥age/2 in men and ≥(age + 10)/2 in women (ESR in millimetres per hour and age in years), and/or C-reactive protein (CRP) ≥15 mg/l. The costs of all tests and procedures and the number of hospitalization days in each patient to reach a diagnosis were calculated using current Dutch tariffs. RESULTS: In group A a diagnosis was reached in 14 of the 46 patients. The mean cost per patient of all the diagnostic procedures was
Asunto(s)
Análisis Costo-Beneficio , Fiebre de Origen Desconocido/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Imagen Multimodal/economía , Tomografía de Emisión de Positrones/economía , Tomografía Computarizada por Rayos X/economía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Adulto JovenRESUMEN
Cardiac resynchronization therapy (CRT) is a disease modifying, device-driven treatment that can reduce morbidity and mortality in patients with heart failure. According to the current guidelines, the indication for CRT is only based on QRS duration and functional class of heart failure. However, a substantial amount of patients do not respond to therapy. In addition, CRT is accompanied by significant cost and potential morbidity. It is therefore vital to improve patient selection for CRT to improve patient outcome and minimize therapy-related complications. In this regard, cardiac sympathetic innervation may be of interest. This review addresses the currently available literature, 9 studies with a total number of 225 patients, on CRT and cardiac innervation scintigraphy with (123)I-metaiodobenzylguanidine.
Asunto(s)
Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/terapia , Corazón/inervación , Sistema Nervioso Simpático/diagnóstico por imagen , Corazón/diagnóstico por imagen , Humanos , Cintigrafía/métodosRESUMEN
AIMS/HYPOTHESIS: South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance. METHODS: We studied 20 healthy men (ten Europids/ten South Asians, BMI 19-25 kg/m(2), age 18-32 years). Following 2 h of cold exposure (16-18°C) after an overnight fast, (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography-computed tomography (CT) and (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV(max)) of (18)F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of (123)I-MIBG. We performed hyperinsulinaemic-euglycaemic clamps to assess insulin sensitivity. Spearman's correlations for SUV(max) of (18)F-FDG and both SQUV of (123)I-MIBG and insulin sensitivity were determined. RESULTS: The median (interquartile range) SUV(max) of (18)F-FDG in South Asians (7.5 [2.2-10.6] g/ml) was not different from the median SUV(max) obtained in Europids (4.5 [2.2-8.4] g/ml; p = 0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of (123)I-MIBG and SUV(max) of (18)F-FDG were positive, both in the total population (ρ = 0.80, p < 0.001) and after stratification by ethnicity (Europids, ρ = 0.65, p = 0.04; South Asians, ρ = 0.83, p = 0.01). CONCLUSIONS/INTERPRETATION: This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Frío , 3-Yodobencilguanidina , Tejido Adiposo Pardo/inervación , Adolescente , Adulto , Asia/etnología , Índice de Masa Corporal , Etnicidad , Europa (Continente)/etnología , Ayuno , Fluorodesoxiglucosa F18 , Técnica de Clampeo de la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Tomografía de Emisión de Positrones/métodos , Sistema Nervioso Simpático/fisiología , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
AIMS: Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection. METHODS AND RESULTS: A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to >35%, any improvement in LVEF of >10%, QRS shortening to <150 ms, or improvement in NYHA class of >1 class. In 33 patients LVEF increased to >35%, QRS decreased <150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to >35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by >10%. No independent predictors were found for QRS shortening to <150 ms or improvement in NYHA class. CONCLUSION: Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT.
Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , 3-Yodobencilguanidina , Anciano , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Cintigrafía , Radiofármacos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Increased systemic levels of myeloperoxidase (MPO) have been reported in patients with acute myocardial ischemia. We studied the association between exercise-induced myocardial ischemia measured by myocardial perfusion scintigraphy (MPS) and the magnitude and time course of changes in MPO levels in humans. METHODS: One hundred and twenty six patients underwent symptom limited exercise MPS. Myocardial ischemia was assessed semi-quantitatively. Plasma samples were taken before the start of exercise (baseline), at maximum exercise and every hour up to 6 h after maximum exercise. RESULTS: Myocardial ischemia was present in 42 (33%) patients. MPO levels rapidly increased during exercise in patients with and without ischemia (to 131% (106-172%) and 145% (121-199%) of baseline, respectively). MPO levels and absolute changes in MPO did not differ between patients with and without ischemia at any time point. None of the patient characteristics, including presence of ischemia, was independently predictive of the absolute increase in MPO levels during exercise. CONCLUSIONS: Exercise related immediate increases in MPO levels do not reflect myocardial ischemia.
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/enzimología , Ejercicio Físico , Isquemia Miocárdica/enzimología , Peroxidasa/sangre , Anciano , Enfermedad de la Arteria Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/fisiopatología , Factores de Tiempo , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. METHODS: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. RESULTS: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). CONCLUSIONS: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.
Asunto(s)
Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Butiratos/administración & dosificación , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Síndrome Metabólico/metabolismo , Delgadez/metabolismo , Administración Oral , Adulto , Ácidos y Sales Biliares/metabolismo , Metabolismo Energético , Ácidos Grasos Volátiles/sangre , Ácidos Grasos Volátiles/metabolismo , Heces/química , Fluorodesoxiglucosa F18 , Microbioma Gastrointestinal , Humanos , Hígado/metabolismo , Masculino , Síndrome Metabólico/tratamiento farmacológico , Proyectos Piloto , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Adulto JovenRESUMEN
OBJECTIVE: In this multicentre study, we investigated the long-term prognostic value of intracoronary derived haemodynamic parameters compared with the results of myocardial perfusion scintigraphy (MPS). METHODS: Patients (n=191) who were referred for angioplasty of a severe lesion in the presence of an intermediate lesion in another coronary artery were included. MPS was performed to determine the presence of reversible perfusion defects in the area of the intermediate lesion. Coronary flow velocity reserve (CFVR), and additionally fractional flow reserve (FFR; n=129), were determined distal to the intermediate lesion; CFVR >/=2.0 and FFR >/=0.75 were considered negative. RESULTS: In total 67 events occurred in 49 patients (3 deaths, 9 MI, 9 CABG, 46 PTCA) during a mean of 793 days follow-up. Event-free survival was 63% for MPS, 79% for CFVR, and 79% for FFR if a negative test result was obtained. The relative risk was 1.2 (not significant) for MPS, 2.2 (p=0.001) for CFVR, and 2.4 (p=0.004) for FFR. CONCLUSION: Selective evaluation of an intermediate lesion using CFVR or FFR allows more adequate risk stratification in patients with multivessel disease than MPS. A CFVR <2.0 or a FFR <0.75 was associated with a significant increase of the occurrence of cardiac events during long-term follow-up, predominantly associated with revascularisation. (Neth Heart J 2007;15:369-74.).
RESUMEN
OBJECTIVE: Normalization of plasma thyrotropin in T4-supplemented patients with thyroidal congenital hypothyroidism (CH) requires elevated plasma FT4-concentrations compared to patients with acquired thyroidal hypothyroidism. We investigated bone mineral density (BMD) in patients with CH. PATIENTS AND METHODS: BMD was measured in 14 adult women with thyroidal CH and nine age-matched female controls. RESULTS: There were no significant differences between patients and controls for femoral neck bone mineral content (BMC) (38.6 vs 37.6 g), BMD (0.98 vs 1.01 g/cm(2)), T-score (0.1 vs 0.3 SD) and z-score (0.1 vs 0.3 SD) and for spine BMC (63.1 vs 71.9 g). The differences in spine BMD (0.97 vs 1.09 g/cm(2)), T-score (-0.7 vs 0.4 SD) and z-score (-0.5 vs 0.6 SD) were significant (p = 0.025, p = 0.023, and p = 0.021, respectively). CONCLUSIONS: Although BMD in patients with CH was slightly lower compared to controls, all scores were within the reference range. This does not support the hypothesis that the upwards shifted plasma FT4-concentrations in patients treated for CH have a deleterious effect on BMD.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Hipotiroidismo Congénito/tratamiento farmacológico , Cuello Femoral/efectos de los fármacos , Vértebras Lumbares/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Tiroxina/uso terapéutico , Absorciometría de Fotón , Adulto , Hipotiroidismo Congénito/metabolismo , Hipotiroidismo Congénito/fisiopatología , Femenino , Cuello Femoral/metabolismo , Humanos , Vértebras Lumbares/metabolismo , Actividad Motora/fisiologíaRESUMEN
BACKGROUND/OBJECTIVE: To compare early invasive treatment with continued pharmacological treatment in patients with diabetes mellitus type 2, mild anginal symptoms and documented myocardial ischaemia. METHODS: Patients with type 2 diabetes mellitus and mild anginal symptoms underwent myocardial perfusion scintigraphy (MPS). Patients with myocardial ischaemia were randomly assigned to early invasive or continued pharmacological treatment. All patients were followed for the occurrence of MACE (death, nonfatal myocardial infarction or hospitalisation for unstable angina pectoris). RESULTS: A total of 156 patients were randomised when the sponsor (ZonMW) prematurely terminated the study because of a slow recruitment rate. With a mean follow-up of 2.1±0.6 years, 9 of 79 patients assigned to early invasive treatment developed MACE compared with 10 of 77 patients randomised to continued pharmacological treatment, annual event rate 5.4 vs. 6.3%, hazard ratio 0.89, 95% CI 0.36 to 2.20, p=0.34. Due to the limited number of included patients and the low event rate, the study did not have sufficient power for the study objective. CONCLUSION: Patients with diabetes mellitus type 2, mild anginal symptoms and documented myocardial ischaemia, under appropriate medical treatment, have a lower than anticipated annual event rate of MACE of ±5 to 6% which questions the beneficial effect of early revascularisation.
RESUMEN
Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening) results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC) 742 mmol/L * 120 min (695-818) vs 641 (504-750), P = 0.036, AUC for insulin did not change, P = 0.575). In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236-96,831) vs 36,448 (25,213-57,711), P = 0.012) and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614-988) vs 644 (568-829), P = 0.017) and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.
RESUMEN
OBJECTIVES: We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND: There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS: Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS: The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS: The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.
Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Circulación Coronaria/fisiología , Enfermedad Coronaria/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Enfermedad Coronaria/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tecnecio Tc 99m SestamibiRESUMEN
OBJECTIVE: Dispersion in refractoriness is considered a major factor in induction and persistence of cardiac arrhythmias. The sympathetic nervous system is known to modulate refractoriness. An index of refractoriness has therefore been assessed in normal and ischaemic myocardium simultaneously at multiple sites, with and without sympathetic stimulation. METHODS: In six dogs on total cardiopulmonary bypass the average interval between local activations was measured during artificially induced ventricular fibrillation from extracellular electrograms simultaneously recorded from 32 ventricular sites. These local ventricular fibrillation intervals may be used as an index of local refractoriness. RESULTS: During regional ischaemia, ventricular fibrillation intervals of ischaemic sites could prolong by up to 60% after 3 min following coronary occlusion. Left stellate ganglion stimulation during ischaemia produced either no response or prolonged the ventricular fibrillation intervals even further at ischaemic sites, whereas ventricular fibrillation intervals at non-ischaemic sites shortened. Dispersion in refractoriness across the ischaemic border increased by 14-59% in individual hearts following sympathetic stimulation during acute, regional ischaemia. CONCLUSIONS: Due to opposite effects on normal and ischaemic myocardium, sympathetic stimulation increases the difference in refractoriness over the ischaemic border. This may enhance the chance for regional conduction block and the propensity to re-entrant arrhythmias.
Asunto(s)
Corazón/fisiopatología , Isquemia Miocárdica/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Enfermedad Aguda , Animales , Puente Cardiopulmonar , Perros , Estimulación Eléctrica , Fibrilación Ventricular/fisiopatologíaRESUMEN
OBJECTIVE: The aim was to examine whether ischaemic preconditioning delays the onset of cellular electrical uncoupling during ischaemia, and whether the effect of preconditioning is mediated by the activation of ATP sensitive K+ channels (IK-ATP). METHODS: Onset of uncoupling, action potential duration (APD80), and conduction velocity were measured in an isolated perfused rabbit papillary muscle. Preconditioning consisted of 10 min occlusion and 10 min reperfusion prior to 40 min sustained ischaemia. Five groups were studied: (1) control (sustained ischaemia only); (2) preconditioning; (3) preconditioning with 20 microM glibenclamide, a blocker of IK-ATP, added for 10 min during the reperfusion period; (4) sustained ischaemia after 15 min perfusion with 20 microM cromakalim (BRL 34915), an opener of IK-ATP; (5) sustained ischaemia after 10 min perfusion with 20 microM glibenclamide without preconditioning. RESULTS: Uncoupling started at 15.0(SEM 0.7) min of ischaemia in the control group and at 22.8(1.5) min after preconditioning (p < 0.001 v control group). Blocking IK-ATP during the preconditioning protocol with glibenclamide abolished the delay of uncoupling: onset was at 14.7(1.2) min. Activation of IK-ATP with cromakalim resulted in uncoupling at 23.3(1.9) min (p < 0.002 v control). Glibenclamide without preconditioning had no effect on uncoupling: onset was at 15.6(1.0) min. APD80 during ischaemia was significantly shorter in the preconditioning and cromakalim groups than in the control group from 5 min of ischaemia onward. In the preconditioning+glibenclamide group and the glibenclamide group APD80 was at no point significantly different from the control group. Conduction velocity during ischaemia decreased to about 70% of baseline after 10 min and was not different between the five groups. CONCLUSIONS: (1) Preconditioning delays the onset of electrical uncoupling; (2) the protective effect of preconditioning may be caused by activation of the IK-ATP channel; (3) the protective effect is associated with reduction of action potential duration, but not with changes of conduction velocity.